Pentose phosphate pathway also called HMP pathway that stands for Hexose Mono- Phosphate Pathway. It is very different from the other pathways, where it neither releases ATP nor consumes ATP during the process. It is a metabolic pathway that occurs in all types of cells and tissues.
In the liver, 30% of glucose is metabolized by the Pentose phosphate pathway. The HMP pathway primarily occurs in the Cytoplasm. It produces NADPH, whose 50% is utilized by the cells in the synthesis of fatty acids. The NADPH molecule also takes part in the oxidative stress homeostasis and synthesis of cytochrome P450 enzymes.
Besides NADPH, HMP pathway also produces trioses, pentoses and hexoses etc. where the production of pentoses helps in the nucleotide synthesis. In this context, you will get to know the meaning, phases (oxidative and non-oxidative phase), and the pentose phosphate pathway’s significance.
Content: Pentose Phosphate Pathway
History
| Year | Scientist | Discovery | Won Nobel prize |
|---|---|---|---|
| 1930s | Otto Warburg | Discovered NADP during the oxidation of glucose 6-phosphate to 6-phosphogluconate | 1931 in physiology or medicine |
| 1950s | Efraim Racker and Fritz Lipmann | Discovered the co-enzyme-A | 1953 in physiology or medicine |
Meaning of Pentose Phosphate Pathway
Pentose phosphate pathway is defined as the metabolic pathway that occurs in all living organisms, and it utilizes the first intermediate product of glycolysis, i.e. Glucose 6-phosphate for the production of NADPH (by the reduction of coenzyme NADP) and a Pentose sugar.
Phases
In the Pentose phosphate pathway, there are two phases, namely oxidative and non-oxidative.
- Oxidative phase: There is oxidation, i.e. a loss of electrons during this phase. It involves the oxidation of glucose 6-phosphate (6-C phosphorylated sugar) into ribulose 5-phosphate (5-C phosphorylated sugar).
- Non-oxidative phase: This phase does not involve the oxidation process. In this phase, ribulose 5-phosphate acts as an intermediate that produces several phosphorylated carbohydrates, which then participates in the synthesis of nucleotides, fatty acid etc.
Pentose Phosphate Pathway Steps
The process of Pentose phosphate pathway can be summarized into two phases, i.e. oxidative and non-oxidative phase.
Oxidative Phase
The oxidative phase of HMP pathway includes the following series of reactions:
Step-1: First, six glucose 6-phosphate molecules will oxidize into 6-phosphoglucolactone in the presence of six coenzyme NADP molecules. Glucose 6-phosphate dehydrogenase catalyzes the conversion of the first step in PPP (Pentose phosphate pathway) and results in the release of six NADPH2 molecules.
Step-2: Then, the six 6-phosphoglucolactone molecules hydrolyze into 6-phosphogluconic acid by the water. Lactonase catalyzes this conversion.
Step-3: Later, six 6-phosphogluconic acid molecules undergo oxidative carboxylation into ribulose 5-phosphate in the presence of six NADP (coenzyme) molecules. An enzyme phosphogluconic acid dehydrogenase catalyzes this conversion. This step releases six NADPH2 molecules.
Non-oxidative Phase
Step-4: After that, six ribulose 5-phosphate molecules undergo isomerization by an enzyme ribulose phosphate 3-epimerase and pentose phosphate isomerase into four xylulose 5-phosphate molecules and two ribose 5-phosphate molecules, respectively.
Step-5: Then, two xylulose 5-phosphate molecules and two ribose 5-phosphate molecules combine to form 2 molecules each of sedoheptulose 7-phosphate and 3-phosphoglyceraldehyde. This reaction is catalyzed by transketolase.
Step-6: After that, two sedoheptulose 7-phosphate molecules and 3- phosphoglyceraldehyde molecules combine to form 2 molecules each of fructose 6-phosphate and erythrose 4-phosphate, respectively. This reaction is catalyzed by transaldolase.
Step-7: Then, a molecule of 3- phosphoglyceraldehyde isomerizes into dihydroxyacetone-phosphate by an enzyme phosphotriose isomerase.
Step-8: Then, a molecule of 3- phosphoglyceraldehyde combines with the dihydroxyacetone-phosphate and converts into fructose 1,6-biphosphate by an enzyme aldolase. Fructose 1, 6-biphosphate further converts into fructose 6-phosphate by an enzyme “phosphatase”.
Step-9: At last, five fructose 6-phosphate molecules convert into five glucose 6-phosphate molecules via an enzyme phosphohexose isomerase.
Net production: The net production in the HMP pathway includes six CO2 molecules and 6 NADPH2 molecules.
Occurrence
Pentose phosphate pathway occurs in all living organisms, but at different sites, for example:
- In animal cell: PPP occurs in the cytosol or cytoplasm of the cell.
- Plant cell: PPP occurs in the plastid.
- In humans: It varies from tissues to tissues.
Significance
Pentose phosphate pathway is an alternative pathway for the carbohydrate degradation or breakdown as it directly oxidizes the glucose 6-phosphate without entering into the glycolysis cycle. Ribulose 5-phosphate being a primary acceptor of CO2, it participates in the CO2 fixation of the photosynthetic organisms during the Calvin-cycle. Ribulose 5-phosphate also helps in the synthesis of Riboflavin.
Another intermediate of PPP is ribose 5-phosphate, which helps in the nucleotide and nucleic acid synthesis. Erythrose 4-phosphate helps in the synthesis of phenylalanine, tryptophan, tyrosine etc. Sedoheptulose 7-phosphate helps in the synthesis of heptoses in the lipopolysaccharide layer of gram-negative bacteria.
The NADPH2 produced in the HMP pathway helps in the reduction biosynthesis of fatty acids, steroid hormones etc. The HMP pathway also plays an essential role in the RBCs to produce NADPH2, as they lack mitochondria. It is the only cytoplasmic pathway that generates NADPH2 as a sole energy source, but not ATP.